Research Interests: Molecular Neurobiology of Drug Abuse: This lab is particularly interested in molecular mechanisms responsible for addictive properties of drugs (mainly cocaine and amphetamines). We are currently conducting experiments from molecule to behavior and from in vitro to in vivo. There are several ongoing projects concerning the role of glutamate receptors in processing enduring synaptic and behavioral plasticity related to addiction. First, in cultured rat striatal neurons, we are investigating the responsible signaling pathways (particularly MAPK/ERK cascades to Elk-1 and CREB) coupling group I metabotropic glutamate receptor signals to nuclear gene expression. The role of mGluR1/5 anchoring protein Homer in connecting mGluR1/5 to specific signaling pathways is also under the investigation. Second, we are interested in the dopamine and glutamate integration and synergy in mediating behavioral plasticity in response to cocaine or amphetamine. Our recent cellular model is a direct binding of dopamine D2 receptors to NMDA receptor NR2B subunits through their intracellular domain. This direct interaction is required for D2 receptors to suppress NMDA receptor function likely in striatopallidal neurons co-expressing D2 and NR2B-containing NMDA receptors and thereby constructing a synergistic motor response to cocaine stimulation. Further experiments are carried out to assess the importance of D2-NR2B binding as well as D1-NR1 binding in behavioral plasticity (behavioral sensitization or reward) in response to chronic exposure to cocaine and amphetamine. Third, a series of in vivo and in vitro experiments are conducted to discover the direct protein-protein interaction between CaMKII and transmitter receptors. We have recently found that CaMKII directly binds to dopamine D2 and D3 receptors muscarinic M4 receptors. These bindings have significant functional implications in phosphorylating and regulating receptor function. We are now working on the identification of new binding targets for several key synaptic protein kinases. Finally, we are conducting in vivo experiments to monitor glutamate receptor trafficking in response to cocaine and amphetamine. Dynamic changes in the number of surface-expressed NMDA receptors due to altered trafficking and sensitized degradation via the ubiquitin-proteasome system are monitored by surface receptor crosslinking assays and other methods. Taken together, the multidisciplinary studies are carried out in this lab to study genes and behaviors critical for drug action.